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ANH-Intl Covid-19 information tracker - Week 14


Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis

 Harri Hemilä, Elizabeth Chalker 

Institution: Department of Public Health, University of Helsinki, POB 41, FI-00014
Helsinki, Finland

Publication date: 7 February 2020

Journal: Journal of Intensive Care

DOI: 10.1186/s40560-020-0432-y. 



Our recent meta-analysis indicated that vitamin C may shorten the length of ICU stay and the duration of mechanical ventilation. Here we analyze modification of the vitamin C effect on ventilation time, by the control group ventilation time (which we used as a proxy for severity of disease in the patients of each trial).


We identified nine potentially eligible trials, eight of which were included in the meta-analysis. We pooled the results of the eight trials, including 685 patients in total, and found that vitamin C shortened the length of mechanical ventilation on average by 14% (P = 0.00001). However, there was significant heterogeneity in the effect of vitamin C between the trials. Heterogeneity was fully explained by the ventilation time in the untreated control group. Vitamin C was most beneficial for patients with the longest ventilation, corresponding to the most severely ill patients. In five trials including 471 patients requiring ventilation for over 10 h, a dosage of 1–6 g/day of vitamin C shortened ventilation time on average by 25% (P < 0.0001).


We found strong evidence that vitamin C shortens the duration of mechanical ventilation, but the magnitude of the effect seems to depend on the duration of ventilation in the untreated control group. The level of baseline illness severity should be considered in further research. Different doses should be compared directly in future trials.


Dietary immune system

Ketogenic Diet: A Role in Immunity

Author: Andrea Pardo MD

Institutions: Division of Neurology, Ann & Robert H. Lurie Children’s Hospital of Chicago, IL;
Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL

Publication date: 3 March 2020

Journal: Pediatric Neurology Briefs

DOI: 10.15844/pedneurbriefs-34-5


The ketogenic diet has been used since the early twentieth century for the treatment of epilepsy. There are multiple mechanisms by which the ketogenic diet exerts its anticonvulsive effect. The increased levels of ketone bodies such as β-hydroxybutyrate have shown to be protective of injury by oxygen reactive species. The modulation and metabolism of GABA systems may also be implicated in the antiseizure mechanism of the ketogenic diet. Additionally, enhanced excitatory neurotransmitter metabolism, effects on synaptic transmission and energy metabolism may be associated to its antiepileptic effect. 

The role of the ketogenic diet in the treatment of superrefractory status epilepticus has been reported in recent literature, particularly its efficacy in immune mediated encephalitis as well as febrile infection-related epilepsy syndrome (FIRES), and new onset refractory status epilepticus (NORSE) [3]. The efficacy of the ketogenic diet on the treatment of this immune mediated status epilepticus
may be mediated by the systemic and metabolic effects of the ketogenic diet on the immune system [4]. Further studies are
required to determine the direct mechanisms by which the ketogenic diet affects inflammation and immunity. The current study highlights molecular pathways of modulation of the immune system that may potentially be harnessed for the treatment of epilepsy. Additionally, it highlights the systemic effects of ketogenic diet identifying a novel immune modulating mechanism.



Hydroxychloroquine use authorised in US & France

The US Food and Drug Administration (FDA) issued emergency authorisation for hydroxychloroquine and chloroquine on 29/03. 

Letter from the FDA to Dr. Rick Bright, PhD, Director, Biomedical Advanced Research and Development Authority (BARDA) authorising use of hydroxychloroquine and chloroquine in the treatment of 2019 coronavirus disease.

Health Minister Olivier Veran said on Monday 23 March, the anti-malarial drug chloroquine can be administered in France to patients suffering from the severest forms of the coronavirus but only under strict supervision.

Coronavirus recovery rate  

The main source for tracking global recovery rates is the John Hopkins dashboard 'Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU)'

The Worldometer coronavirus tracker also includes recovery rates

The recovery rate in Korea as 26 March 2020 is nearly 45%

Comorbidities in UK

The Intensive care national audit & research centre (ICNARC) report on COVID-19 in critical care on the first 775 patients critically ill as at 26/03 with confirmed COVID-19.

The report contains data on all confirmed COVID-19 cases reported to ICNARC up to midnight on 26 March 2020 from critical care units participating in the Case Mix Programme (all NHS adult, general intensive care and combined intensive care/high dependency units in England, Wales and Northern Ireland, plus some specialist and non-NHS critical care units).

Number of coronavirus (COVID-19) cases and risk in the UK

Data on the latest number of coronavirus (COVID-19) cases and risk level in the UK from the UK government.

COVID-19 origins

The proximal origin of SARS-CoV-2

Authors: Andersen KG et al

Institutions: Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA
Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
Center for Infection and Immunity, Mailman School of Public Health of Columbia University, New York, NY, USA
Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, Australia
Tulane University, School of Medicine, Department of Microbiology and Immunology, New Orleans, LA, USA

Publication date: 17 March 2020

Journal: Nature Medicine

DOI: 10.1038/s41591-020-0820-9

SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms6. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.


COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses

Authors: Shereen MA et al

Institutions: The Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
College of Life Sciences, Wuhan University, Wuhan, PR China

Publication date: 16 March 2020

Journal: Journal of Advanced Research

DOI: 10.1016/j.jare.2020.03.005

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.


Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic

Authors: Boni MF et al

Publication date: 31 March 2020

Journal: bioRxiv - the prepring server for biology

DOI: 10.1101/2020.03.30.015008

There are outstanding evolutionary questions on the recent emergence of coronavirus SARS-CoV-2/hCoV-19 in Hubei province that caused the COVID-19 pandemic, including (1) the relationship of the new virus to the SARS-related coronaviruses, (2) the role of bats as a reservoir species, (3) the potential role of other mammals in the emergence event, and (4) the role of recombination in viral emergence. Here, we address these questions and find that the sarbecoviruses -- the viral subgenus responsible for the emergence of SARS-CoV and SARS-CoV-2 -- exhibit frequent recombination, but the SARS-CoV-2 lineage itself is not a recombinant of any viruses detected to date. In order to employ phylogenetic methods to date the divergence events between SARS-CoV-2 and the bat sarbecovirus reservoir, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were consistent for all three recombination-free alignments and robust to two different prior specifications based on HCoV-OC43 and MERS-CoV evolutionary rates. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% HPD: 1879-1999), 1969 (95% HPD: 1930-2000), and 1982 (95% HPD: 1948-2009). Despite intensified characterization of sarbecoviruses since SARS, the lineage giving rise to SARS-CoV-2 has been circulating unnoticed for decades in bats and been transmitted to other hosts such as pangolins. The occurrence of a third significant coronavirus emergence in 17 years together with the high prevalence and virus diversity in bats implies that these viruses are likely to cross species boundaries again.



How coronavirus mutations can track its spread—and disprove conspiracies

Article from National Geographic

Published: 29 March 20

Think of the open-source project Nextstrain.org as an outbreak museum. Labs around the world contribute genetic sequences of viruses collected from patients, and Nextstrain uses that data to paint the evolution of epidemics through global maps and phylogenetic charts – the family trees for viruses.

So far, Nextstrain has crunched nearly 1,500 genomes from the new coronavirus, and the data already show how this virus is mutating—every 15 days, on average—as the COVID-19 pandemic rages around the world.

Icelandic scientists are reported to have found 40 mutations of the coronavirus

Financial impact

The economic impact of coronavirus: analysis from Imperial experts

Academics and researchers from Imperial College Business School have offered reactions and analysis of the impact of coronavirus on business and the economy, as well as the responses of governments and central banks

The UN says the coronavirus pandemic is the greatest challenge it's faced since its formation as UN chief launches new plan to counter the potentially devastating socio-economic impacts of COVID-19

Case fatality rate

Covid-19 - Navigating the Uncharted

Author: Fauci AS et al

Publication date: 26 March 2020

Journal: The New England Journal of Medicine



"...If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1%."

Comments from Dr Fauci during CNN's State of Union 29/03

Link to watch recording of State of Union

Severity of pandemic

Estimates of the severity of coronavirus disease 2019: a model-based analysis

Authors: Verity R PhD et al

Publication date: 30 March 2020

Institutions:MRC Centre for Global Infectious Disease Analysis, Abdul Latif Jameel Institute for Disease and Emergency Analytics, and Department of Infectious Disease Epidemiology, Imperial College London, London, UK

Journal: The Lancet Infectious Diseases

DOI: 10.1016/S1473-3099(20)30243-7

Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older.


These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death.


Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries

Authors: Flaxman S et al

Publication date: 30 March 2020

Institutions: Imperial College COVID-19 Response Team

New modelling study from Imperial College estimating between 20,000 and 120,000 deaths will probably have been avoided by end March using shutdowns. They estimate between 7m and 43m individuals have been infected across the 11 countries representing between 1.88% and 11.45% of the population.



Timely blood glucose management for the outbreak of 2019 novel coronavirus disease (COVID-19) is urgently needed

Authors: Wang A et al

Publication date: 01 April 2020

Institution: Department of Endocrinology, PLA Strategic Support Force Characteristic Medical Center (The 306th Hospital of PLA), Beijing 100101, China

Journal: Diabetes research and clinical practice

DOI: 10.1016/j.diabres.2020.108118

The population is generally susceptible to this coronavirus, and the elderly and those with certain underlying diseases are more vulnerable to SARS-CoV-2, including hypertension and diabetes [1, 2]. It was reported that the overall proportion of diabetes in COVID-19 was from 5.3% to 20% [1, 2, 3, 4, 5, 6]. Due to compromised innate immune response, diabetic patients exist increased susceptibility and enhanced disease severity following SARS-CoV-2 infection. In addition, COVID-19 with diabetes has much more potential to progress rapidly with acute respiratory distress syndrome and septic shock, which may be eventually followed by multiple organ failure. Comorbid diabetes was associated with much more intensive care unit (ICU) admission. Compared with patients who did not receive ICU care, ICU patients with virus infection were more likely to have underlying diabetes (22.2% vs 5.9%) [1]. Clinical data shown that the mortality of COVID-19 patients was from 2.3% to 15% [1, 2, 3, 6]. Remarkably, presence of diabetes is associated with increased mortality.


Covid-19 infection in people with diabetes

Authors: Sten Madsbad

Publication date: 01 April 2020

Institution: Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark

Source: Touch Endocrinology

Diabetes is a risk factor for hospitalisation and mortality of the COVID-19 infection. Diabetes was a comorbidity in 22% of 32 non-survivors in a study of 52 intensive care patients.2 In another study of 173 patients with severe disease, 16.2% had diabetes, and in further study of 140 hospitalised patients, 12% had diabetes.3,4 When comparing intensive care and non-intensive care patients with COVID-19, there appears to be a twofold increase in the incidence of patients in intensive care having diabetes.11 Mortality seems to be about threefold higher in people with diabetes compared with the general mortality of COVID-19 in China.2–11

The number of comorbidities is a predictor of mortality in COVID-19. In addition to diabetes, the other common comorbidities were hypertension, in about 20% of cases, cardiovascular disease (16%), and lung disease (6%).2–11 Indeed, people with diabetes are a high-risk group for severe disease. Notably, diabetes was also a risk factor for severe disease and mortality in the previous SARS, MERS (Middle East respiratory syndrome) coronavirus infections and the severe influenza A H1N1 pandemic in 2009.


Clinical Findings of Patients with Coronavirus Disease 2019 in Jiangsu Province, China: A Retrospective, Multi-Center Study

Authors: Huan R et al

Publication date: 10 March 2020

Journal: Preprints with The Lancet

DOI: 10.2139/ssrn.3548785

In this case series in Jiangsu Province, COVID-19 patients have less severe symptoms and have better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m 2 and a known history of type 2 diabetes are independent risk factors of severe illness in patients with COVID-19.


Clinical and epidemiological characteristics

Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):A multi-center study in Wenzhou city, Zhejiang, China

Authors: Yang W et al

Publication date: 26 February 2020

Journal: Journal of Infection

DOI: 10.1016/j.jinf.2020.02.016

Most patients presented with a mild infection in our study. The imaging pattern of multifocal peripheral ground glass or mixed opacity with predominance in the lower lung is highly suspicious of COVID-19 in the first week of disease onset. Nevetheless, some patients can present with a normal chest finding despite testing positive for COVID-19.


Epidemiological and clinical characteristics of 17 hospitalised patients with 2019 novel coronavirus infections outside Wuhan, China

Authors: Li J et al

Publication date: 12 February 2020

Institutions: Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China. 2Division of infectious diseases, Dazhou Central Hospital, Dazhou, Sichuan, China

Journal: medRxiv preprint

DOI: 10.1101/2020.02.11.20022053

An increasing number of cases of novel coronavirus pneumonia (NCP) infected with 2019-nCoV have been identified in Wuhan and other cities in China, since December 2019. We analyzed data on the 17 confirmed cases in Dazhou to provide the epidemiologic characteristics of NCP outside Wuhan. Among them, 12 patients were still quarantined in the hospital, 5 patients were discharged NCP patients according to the national standards. Compared with non-discharged NCP patients, the discharged NCP patients had younger ages. Moreover, discharged NCP patients had higher heart rate, lymphocytes levels and monocytes levels than non-discharged NCP patients on admission to the hospital. Notably, all of 17 patients had abnormal increased C-reactive protein levels, and 16 patients had abnormal computed tomography images. This study provided some information that younger age, higher lymphocytes levels and monocytes levels at the diagnoses of 2019-nCoV may contributed to faster recovery and better therapeutic outcome.



Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan

Authors: Wang M et al

Publication date: 18 February 2020

Institutions: Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China. 2Division of infectious diseases, Dazhou Central Hospital, Dazhou, Sichuan, China

Journal: medRxiv preprint

DOI: 10.1101/2020.02.12.20022327

Interpretation: Clinical testing methods for 2019-nCoV require improvement. Importantly, 5.8% of 2019-nCoV infected and 18.4% of non-2019-nCoV-infected patients had other pathogen infections. It is important to treat combined infections and perform rapid screening to avoid cross-contamination of patients. A test that quickly and simultaneously screens as many pathogens as possible is needed.


Co-infection with SARS-CoV-2 and Influenza A Virus in Patient with Pneumonia, China

Authors: Wu X et al

Publication date: 11 March 2020

Institutions: China-Japan Friendship Hospital, Beijing, China, The Sixth Medical Center of PLA General Hospital, Beijing, Weifang No. 2 People’s Hospital, Weifang, China Vision Medicals Co., Ltd., Guangzhou, China

Journal: Emerging Infectious Diseases

DOI: 10.3201/eid2606.200299

We report co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus in a patient with pneumonia in China. The case highlights possible co-detection of known respiratory viruses. We noted low sensitivity of upper respiratory specimens for SARS-CoV-2, which could further complicate recognition of the full extent of disease.




Tackling 'misinformation'

Blocking information on COVID-19 can fuel the spread of misinformation

Publication: Nature

Author: Heidi J Larson

Date: 30 March 2020

Two years ago, in a response to false information on social-media platforms, the United Nations special rapporteur on the promotion and protection of the right to freedom of opinion and expression condemned governments that disallow free speech in the name of public order. The report of the special rapporteur gave as an example the Chinese Cybersecurity Law of 2016, which “reinforces vague prohibitions against the spread of ‘false’ information that disrupts ‘social or economic order’, national unity or national security.”

As the world faces the COVID-19 pandemic, we are seeing what problems this suppression can wreak. What if the information deemed by government authorities as disrupting social order is not ‘false’, but instead a life-saving clue? When governments or their leaders repress information in hope of calming anxious publics, or deliberately release supposedly reassuring misinformation, they risk undermining their own credibility and their abilities to help people to counter real health threats.

Recording accuracy

Are deaths of people with Covid-19 being accurately recorded?

Recording of Italian deaths

Publication: Off Guardian

Date: 23 March 2020

According to Prof Walter Ricciardi – “the way in which we code deaths in our country is very generous in the sense that all the people who die in hospitals with the coronavirus are deemed to be dying of the coronavirus.” “On re-evaluation by the National Institute of Health, only 12 per cent of death certificates have shown a direct causality from coronavirus, while 88 per cent of patients who have died have at least one pre-morbidity - many had two or three,” he says.

Article from Gabriela Segura MD

Publication: Health Matrix

Date: 29 March 2020

'A doctor on the front-line' in the 'war against COVID-19' questioning the way deaths are being recorded 

Vitamin C

Publication: Nutraingredients Asia

Date: 31 March 2020

Health authorities in the Philippines are buying vitamin C for school children to support their immune system.


Publication: CNN

Date: 29 March 2020

102 yr old Italian woman recovers